The Drosophila protein Wunen repels migrating germ cells

Zhang, Nian; Zhang, Jiaping; Purcell, Karen J.; Cheng, Yan; Howard, Kenneth I.

doi:10.1038/385064a0

Cited by 196 publications

(152 citation statements)

References 22 publications

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“…We thus cloned a human counterpart of rat Dri42 in an attempt to characterize PAP isozymes. In addition, Drosophila Wunen protein, which was discovered as a repulsive gene product responsible for regulating the germ cell migration in the embryo (29), shares 39 and 34% identical sequences with PAP-2a and PAP-2b, respectively. The four mammalian PAP homologs contained a single conserved N-glycosylation site, and PAP-2a and -2b were indeed confirmed to be glycoproteins as will be described later.…”

Section: Resultsmentioning

confidence: 99%

“…Rat Dri42 has been cloned as a gene induced upon epithelial differentiation in the small intestine (30). It was also noted that the two human PAPs exhibit a significant similarity to Drosophila Wunen, which regulates the germ cell migration (29). The sequencing of the mammalian PAPs thus unexpectedly disclosed important roles of the type 2 PAPs in basic biological functions such as cell migration, differentiation, and growth.…”

Section: B Lane 5)mentioning

confidence: 99%

“…The cloned enzyme is a novel glycoprotein exhibiting a channel-like structure with six putative transmembrane domains. We soon noticed (28) that the amino acid sequence of the mouse PAP is 34 and 48% identical to those of Drosophila Wunen protein (29) and rat Dri42 protein (30), respectively. The Wunen and Dri42 have been cloned as gene products involved in the regulation of germ cell migration (29) and in epithelial differentiation (30), respectively.…”

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confidence: 99%

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Cloning and Characterization of Two Human Isozymes of Mg2+-independent Phosphatidic Acid Phosphatase

Kai

Wada

Imai

et al. 1997

Journal of Biological Chemistry

175

211

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We obtained two human cDNA clones encoding phosphatidic acid phosphatase (PAP) isozymes named PAP-2a (M r ‫؍‬ 32,158) and -2b (M r ‫؍‬ 35, 119), both of which contained six putative transmembrane domains. Both enzymes were glycosylated and cleaved by N-glycanase and endo-␤-galactosidase, thus suggesting their post-Golgi localization. PAP-2a and -2b shared 47% identical sequence and were judged to be the human counterparts of the previously sequenced mouse 35-kDa PAP(83% identity) and rat Dri42 protein (94% identity), respectively. Furthermore, the sequences of both PAPs were 34 -39% identical to that of Drosophila Wunen protein. In view of the functions ascribed to Wunen and Dri42 in germ cell migration and epithelial differentiation, respectively, these findings unexpectedly suggest critical roles of PAP isoforms in cell growth and differentiation. Although the two PAPs hydrolyzed lysophosphatidate and ceramide-1-phosphate in addition to phosphatidate, the hydrolysis of sphingosine-1-phosphate was detected only for PAP-2b. PAP-2b was expressed almost ubiquitously in all human tissues examined, whereas the expression of PAP-2a was relatively variable, being extremely low in the placenta and thymus. In HeLa cells, the transcription of PAP-2a was not affected by different stimuli, whereas PAP-2b was induced (up to 3-fold) by epidermal growth factor. These findings indicate that despite structural similarities, the two PAP isozymes may play distinct functions through their different patterns of substrate utilization and transcriptional regulation.Phosphatidic acid phosphatase (PAP) 1 (EC 3.1.3.4) supplies diacylglycerol (DG) in glycerolipid biosynthesis by dephosphorylating phosphatidic acid (PA) (1). Since both DG (2) and PA (3) are potent signaling molecules, PAP plays an important role in cellular signal transduction in addition to lipid biosynthesis (4). In signaling systems mediated by phospholipase D (5), liberated PA is generally converted, albeit to different extents, to DG by the action of PAP (6 -8), thus suggesting that PAP contributes to the control of the relative balance of the two lipid second messengers.There exist two forms of mammalian PAP that can be distinguished with respect to subcellular localization and enzymologic properties (9). So far, distinct functions have been ascribed to the two forms of PAP. The type 1 PAP, a Mg 2ϩ -dependent and N-ethylmaleimide-sensitive enzyme, is considered to be primarily involved in lipid synthesis based on its translocation from the cytosol to microsomes upon stimulation of cellular triacylglycerol synthesis (10 -12). In this context, a recent work showed using a novel enzyme inhibitor that the type 1 PAP indeed participated in triacylglycerol synthesis in mouse macrophages (13). On the other hand, the type 2 PAP, a Mg 2ϩ -independent and N-ethylmaleimide-insensitive enzyme, has been postulated to participate in cellular signal transduction mediated by phospholipase D. The finding that the activities of the type 2 PAP and phospholipase D were decreased in a c...

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Section: Resultsmentioning

confidence: 99%

Section: B Lane 5)mentioning

confidence: 99%

mentioning

confidence: 99%

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Cloning and Characterization of Two Human Isozymes of Mg2+-independent Phosphatidic Acid Phosphatase

Kai

Wada

Imai

et al. 1997

Journal of Biological Chemistry

175

211

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“…These observations, while speculative, are consistent with an integral plasma membrane localization of the enzyme such as has been proposed (29). Similarly, the PA metabolizing enzyme, PA phosphatase 2, is predicted to have five or six transmembrane domains and is thought to localize to the plasma membrane (30). It will be of interest to examine the spatial relationship between the two enzymes; perhaps they comprise part of a multienzyme locus that mediates LPA/PA metabolism.…”

Section: Discussionmentioning

confidence: 99%

Human Lysophosphatidic Acid Acyltransferase

Eberhardt

Gray

Tjoelker

1997

Journal of Biological Chemistry

114

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Lysophosphatidic acid (1-acyl-sn-glycero-3-phosphate (LPA)) is a phospholipid with diverse biological activities. The mediator serves as an intermediate in membrane phospholipid metabolism but is also produced in acute settings by activated platelets. LPA is converted to phosphatidic acid, itself a lipid mediator, by an LPA acyltransferase (LPAAT). A human expressed sequence tag was identified by homology with a coconut LPAAT and used to isolate a full-length human cDNA from a heart muscle library. The predicted amino acid sequence bears 33% identity with a Caenorhabditis elegans LPAAT homologue and 23-28% identity with plant and prokaryotic LPAATs. Recombinant protein produced in COS 7 cells exhibited LPAAT activity with a preference for LPA as the acceptor phosphoglycerol and arachidonyl coenzyme A as the acyl donor. Northern blotting demonstrated that the mRNA is expressed in most human tissues including a panel of brain subregions; expression is highest in liver and pancreas and lowest in placenta. The human LPAAT gene is contained on six exons that map to chromosome 9, region q34.3.

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“…Among the dystrophic phenotypes observed in Drosophila is a visible wing vein defect (Christoforou et al, 2008;Kucherenko et al, 2008), which was previously used to screen for suppressors (Kucherenko et al, 2008). One of the suppressors of the wing vein defect was mutant of wunen, a lipid phosphate phosphatase, which was initially identified as a gene required for proper germ cell migration in the Drosophila embryo (Zhang et al, 1996;Zhang et al, 1997;Starz-Gaiano et al, 2001). There are three lipid phosphate phosphatases in mammals: LPP1, LPP2 and LPP3 (also known as PPAP2A, PPAP2C and PPAP2B, respectively).…”

Section: Introductionmentioning

confidence: 99%

Genetic elevation of Sphingosine 1-phosphate suppresses dystrophic muscle phenotypes in Drosophila

et al. 2013

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SUMMARYDuchenne muscular dystrophy is a lethal genetic disease characterized by the loss of muscle integrity and function over time. Using Drosophila, we show that dystrophic muscle phenotypes can be significantly suppressed by a reduction of wunen, a homolog of lipid phosphate phosphatase 3, which in higher animals can dephosphorylate a range of phospholipids. Our suppression analyses include assessing the localization of Projectin protein, a titin homolog, in sarcomeres as well as muscle morphology and functional movement assays. We hypothesize that wunen-based suppression is through the elevation of the bioactive lipid Sphingosine 1-phosphate (S1P), which promotes cell proliferation and differentiation in many tissues, including muscle. We confirm the role of S1P in suppression by genetically altering S1P levels via reduction of S1P lyase (Sply) and by upregulating the serine palmitoyl-CoA transferase catalytic subunit gene lace, the first gene in the de novo sphingolipid biosynthetic pathway and find that these manipulations also reduce muscle degeneration. Furthermore, we show that reduction of spinster (which encodes a major facilitator family transporter, homologs of which in higher animals have been shown to transport S1P) can also suppress dystrophic muscle degeneration. Finally, administration to adult flies of pharmacological agents reported to elevate S1P signaling significantly suppresses dystrophic muscle phenotypes. Our data suggest that localized intracellular S1P elevation promotes the suppression of muscle wasting in flies.

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The Drosophila protein Wunen repels migrating germ cells

Cited by 196 publications

References 22 publications

Cloning and Characterization of Two Human Isozymes of Mg2+-independent Phosphatidic Acid Phosphatase

Cloning and Characterization of Two Human Isozymes of Mg2+-independent Phosphatidic Acid Phosphatase

Human Lysophosphatidic Acid Acyltransferase

Genetic elevation of Sphingosine 1-phosphate suppresses dystrophic muscle phenotypes in Drosophila

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